Project Summary/Abstract Feasibility This study will assess the feasibility of enrolling eligible patients (pts), and of enrolled pts undergoing low-volume or high-volume hemofiltration (HF) for at least 80% of 48 hours among those resuscitated from out-of-hospital cardiac arrest (OOHCA). HF washes the blood to remove the blood inflammatory factors that are associated with reperfusion injury (RI), organ dysfunction and death. Background RI occurs during restoration of circulation after OOHCA. It is associated with substantial release of pro-inflammatory cytokines. This leads to microcirculatory dysfunction within 24 hours. Cardiac function improves but vascular permeability increase over the next three days, predisposing to neurologic injury, multiple organ dysfunction and death. HF is a technique of removing extracellular fluid that is similar to hemodialysis. This extracellular fluid includes the solutes, which contain the inflammatory factors released during RI. We propose to evaluate the feasibility of using HF technology (Diapact, B Braun Medical Inc., Bethlehem, PA) to reduce RI after resuscitation from CA. Methods Design- Individual randomized trial. Population- Adults with spontaneous circulation after OOHCA with any initial rhythm. Excluded: do not attempt resuscitation orders; major pre-arrest neurological dysfunction; another reason to be comatose; blunt, penetrating or other injury; thrombocytopenia or coagulopathy; inferior vena cava filter in situ; known pregnancy; hemodynamic instability; allergy to acetaminophen; prior enrollment in the study. Interventions- randomized to control versus low-HF versus high-volume HF for 48 hours. Control and intervention pts shall receive intravenous fluids, vasopressor or vasodilator treatment as required to maintain a central venous pressure of 8-12 mm Hg and a mean arterial pressure between 100-120 mm Hg. Concurrent intervention will include initiation and maintenance of therapeutic hypothermia in pts who are unconscious. Analyses- The proportion of eligible pts who are enrolled, and of intervention pts who undergo HF for at least 80% of 48 hours will be summarized as binomial proportions. Clinical measures will be summarized descriptively. Sample Size- we anticipate that about 60 pts will meet our inclusion criteria during a 12 month enrollment period. We shall enroll 30 pts (10 per group). Relevance this trial will prove that HF is feasible in pts resuscitated from OOHCA. The design of a subsequent trial to test the effect of HF upon survival, neurologic function and health-related QOL will be modified based on the results of this pilot study.